Association of BMI trajectories with cardiometabolic risk among low-income Mexican American children.

BACKGROUND: The aim of this study was to identify distinct trajectories of BMI growth from 2 to 7.5 years and examine their associations with markers of cardiometabolic risk at age 7.5 years among a sample of low-income Mexican American children. METHODS: This longitudinal cohort study recruited 322 mother-child dyads to participate prenatally and at child age 2, 3, 4.5, 6, and 7.5 years. Child height/weight, waist circumference, and blood pressure were assessed at each time point. Blood was collected from child at 7.5 years. RESULTS: Covarying for birthweight, three BMI trajectories were identified: Low-Stable BMI (73% of the sample), High-Stable BMI (5.6% of the sample), and Increasing BMI over time (21.4% of the sample). The High-Stable and Increasing BMI classes had higher waist circumference and systolic blood pressure and lower HDL-c than the Low-Stable BMI class (ps < 0.05). Among children with BMIs below the 85th percentile, 16% had three or more cardiometabolic risk indicators. CONCLUSIONS: BMI classes were consistent with existing literature. For youth, standard medical practice is to examine cardiometabolic risk indicators when BMI is high; however, this practice would miss 16% of youth in our sample who exhibit cardiometabolic risk but do not screen in based on BMI. IMPACT: Research indicates Mexican American youth are at risk for cardiometabolic dysregulation relative to other ethnic groups, yet there is a paucity of longitudinal research. An Increasing BMI and a High-Stable BMI class were associated with larger waist circumference, higher systolic blood pressure, and lower HDL cholesterol than the Low-Stable BMI class. BMI trajectories in childhood predict cardiometabolic risk indicators. As the sole screener for deciding when to test cardiometabolic indicators, BMI alone will miss some children exhibiting cardiometabolic dysregulation.

Guillain-Barre syndrome before and during the COVID-19 pandemic in a referral center of Mexico.

BACKGROUND: During the COVID-19 pandemic, an increase in the number of Guillain-Barre syndrome (GBS) cases has been reported. OBJECTIVE: To describe the clinical characteristics and prognosis of patients with GBS before and during the COVID-19 pandemic. MATERIAL AND METHODS: Prospective cohort of GBS patients divided in two subgroups: before (2018-2019) and during (2020-2021) the COVID-19 pandemic. Clinical and paraclinical characteristics, as well as deaths, were recorded. A good prognosis was defined as independent ambulation recovery at three months. RESULTS: Two-hundred and one patients were included (123 during and 78 before the pandemic), out of whom 69% were males; age was 45 ± 16 years, and there was 2.5% of in-hospital deaths. During the pandemic, a higher frequency of the demyelinating variant (50%), bulbar cranial nerves involvement (44% vs. 28%), prior history of vaccination (16% vs. 0%), and a lower MRC score (30 ± 16.7 vs. 34.3 ± 17.7) were documented. An increase in the number of cases was observed from July to September (38 vs. 13). There were no significant differences in independent ambulation recovery or in the number of deaths. CONCLUSIONS: During the COVID-19 pandemic, a higher number of GBS cases were treated, out of which 16% were associated with the SARS-CoV-2 vaccine; patients treated during the pandemic did not have a worse prognosis.

ANTECEDENTES: Durante la pandemia de COVID-19 se ha reportado incremento de casos de síndrome de Guillain-Barré (SGB). OBJETIVO: Describir características clínicas y pronóstico de pacientes con SGB antes y durante la pandemia de COVID-19. MATERIAL Y MÉTODOS: Cohorte prospectiva de pacientes con SGB estratificados en dos subgrupos: antes (2018-2019) y durante (2020-2021) la pandemia de COVID-19. Se registraron características clínicas, paraclínicas y defunciones. Se definió como buen pronóstico a la recuperación de la marcha independiente a los tres meses. RESULTADOS: Se incluyeron 201 pacientes (123 durante la pandemia y 78 antes), 69 % del sexo masculino, edad de 45 ± 16 años, 2.5 % de muertes intrahospitalarias. Durante la pandemia se observó mayor frecuencia de la variante desmielinizante (50 %), afección de nervios craneales bulbares (44 % versus 28 %), antecedente de vacunación (16 % versus 0 %) y menor puntuación en la escala MRC (30 ± 16.7 versus 34.3 ± 17.7); se observó aumento de casos de julio a septiembre (38 versus 13). No existieron diferencias significativas en la recuperación de la marcha independiente y número de defunciones. CONCLUSIONES: Durante la pandemia se atendió mayor número de casos de SGB, 16 % asociado a la vacuna contra SARS-CoV-2; los pacientes no presentaron peor pronóstico.

The Educational Quality of Laparoscopic Right Hemicolectomy Videos on YouTube.

Introduction. Surgical technique videos are an important part of surgical fellows' education. YouTube has been identified as the preferred source of educational videos among trainees. The aim of this article is to objectively evaluate the quality of the 50 most viewed videos on YouTube concerning right laparoscopic hemicolectomy using LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS). We hypothesized that the number of likes or views will not necessarily reciprocate with the educational content. Materials and methods. This observational study started with a YouTube search under the words "laparoscopic right hemicolectomy", "right colectomy", and "right hemicolectomy". The 50 most viewed videos with an English title were chosen. Video characteristics and LAP-VEGaS score were analyzed by four colorectal surgery fellows from a tertiary center in Mexico City. Results. Right hemicolectomy videos were reviewed; there was no correlation between the LAP-VEGaS score and the view ratio, the like ratio, or the video power index. The LAP-VEGaS score was significantly higher among videos uploaded by medical associations, journals, or commercial when compared with videos uploaded by doctors/physicians or academic associations. Conclusion. Educational quality in right laparoscopic hemicolectomy videos did not reciprocate with their educational quality, but it agrees significantly with the video uploading source. Low educational quality was identified among the videos underscoring the need to endorse peer-reviewed video channels.

Models to predict live weight from heart girth in crossbred beef heifers.

The objective of this study was to develop and evaluate linear, quadratic, and exponential mathematical models to predict live weight (LW) from heart girth (HG) in crossbred heifers raised in tropical humid conditions in Mexico. Live weight (363.32 ± 150.88 kg) and HG (166.83 ± 24.88 cm) were measured in 400 heifers aged between 3 and 24 months. Linear and non-linear regression was used to construct the prediction models. The goodness of fit of the models was evaluated using the Akaike information criterion (AIC), the Bayesian information criterion (BIC), coefficient of determination (R2), mean squared error (MSE), and root MSE (RMSE). In addition, the developed models were evaluated through internal and external cross-validation (k-folds) using independent data. The ability of the fitted models to predict the observed values was evaluated based on the root mean square error of prediction (RMSEP), R2, and mean absolute error (MAE). The correlation coefficient between LW and HG was r = 0.98 (P < 0.001). The quadratic model showed the lowest values of MAE (736.57), RMSEP (27.13), AIC (3783.95), and BIC (3799.91). Additionally, this model exhibited better goodness-of-fit values regarding external and internal validation criteria (higher R2 and lower RMSEP and MAE), thus having better predictive performance. The RMSE represented about 8% of the observed LW. Heart girth is highly correlated (r = 0.98) with LW. The quadratic model showed a high predictive capacity for crossbred heifers kept in tropical conditions.

Guillain-Barré Syndrome in Mexico: An Updated Review Amid the Coronavirus Disease 2019 ERA.

Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis and if not diagnosed and treated timely, a significant cause of long-term disability. Incidence in Latin America ranges from 0.71 to 7.63 cases/100,000 person-years. Historically, GBS has been linked to infections (mainly gastrointestinal by Campylobacter jejuni) and vaccines (including those against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]); however, a trigger cannot be detected in most cases. Regarding SARS-CoV-2, epidemiological studies have found no association with its development. Acute motor axonal neuropathy is the most common electrophysiological variant in Mexico and Asian countries. Intravenous immunoglobulin or plasma exchanges are still the treatment cornerstones. Mortality in Mexico can be as high as 12%. Avances in understanding the drivers of nerve injury in GBS that may provide the basis for developing targeted therapies have been made during the past decade; despite them, accurate criteria for selecting patients requiring acute treatment, prognostic biomarkers, and novel therapies are still needed. The newly-developed vaccines against SARS-CoV-2 have raised concerns regarding the potential risk for developing GBS. In the midst of coronavirus disease 2019 and vaccination campaigns against SARS-CoV-2, this review discusses the epidemiology, clinical presentation, management, and outcomes of GBS in Mexico.

Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms.

Due to the scarcity of therapeutic approaches for COVID-19, we investigated the antiviral and anti-inflammatory properties of curcumin against SARS-CoV-2 using in vitro models. The cytotoxicity of curcumin was evaluated using MTT assay in Vero E6 cells. The antiviral activity of this compound against SARS-CoV-2 was evaluated using four treatment strategies (i. pre-post infection treatment, ii. co-treatment, iii. pre-infection, and iv. post-infection). The D614G strain and Delta variant of SARS-CoV-2 were used, and the viral titer was quantified by plaque assay. The anti-inflammatory effect was evaluated in peripheral blood mononuclear cells (PBMCs) using qPCR and ELISA. By pre-post infection treatment, Curcumin (10 µg/mL) exhibited antiviral effect of 99% and 99.8% against DG614 strain and Delta variant, respectively. Curcumin also inhibited D614G strain by pre-infection and post-infection treatment. In addition, curcumin showed a virucidal effect against D614G strain and Delta variant. Finally, the pro-inflammatory cytokines (IL-1ß, IL-6, and IL-8) released by PBMCs triggered by SARS-CoV-2 were decreased after treatment with curcumin. Our results suggest that curcumin affects the SARS-CoV-2 replicative cycle and exhibits virucidal effect with a variant/strain independent antiviral effect and immune-modulatory properties. This is the first study that showed a combined (antiviral/anti-inflammatory) effect of curcumin during SARS-CoV-2 infection. However, additional studies are required to define its use as a treatment for the COVID-19.

Influence of Muscle Mass Area and Visceral Obesity on 30-day Mortality After Colorectal Surgery with Primary Anastomosis.

BACKGROUND: Muscle mass and visceral fat may be assessed at the level of the third lumbar vertebra (L3) in computed tomography (CT). Both variables have been related with adverse surgical outcomes. OBJECTIVE: The objective of the study was to study the association of skeletal muscle index (SMI) and visceral fat area (VFA) with 30-day mortality in colorectal surgery. METHODS: This is a retrospective cohort study conducted at a tertiary referral hospital in Mexico City. Patients who underwent colorectal surgery with primary anastomosis from January 2007 to December 2018 were included in the study. Their preoperative CT scans were analyzed with the NIH ImageJ software at the level of the third lumbar vertebra to determine their SMI (L3-SMI) and the VFA. Logistic regression analysis (adjusted by surgery anatomical location) was used to determine the association between these variables and surgical 30-day mortality. RESULTS: A total of 548 patients were included; 30-day mortality was 4.18% (23 patients). On univariable analysis, L3-SMI, low SMI, anastomosis leak, pre-operative albumin, estimated blood loss, age, steroid use, Charlson comorbidity index score >2, and type of surgery were associated with 30-day mortality. On multivariable analysis, low SMI remained an independent risk factor with an odds ratio of 4.74, 95% confidence interval 1.22-18.36 (p = 0.02). CONCLUSION: Low SMI was found to be an independent risk factor for 30-day mortality in patients submitted to colorectal surgery with a primary anastomosis, whether for benign or malignant diagnosis. VFA was not associated with 30-day mortality.

Effect of high doses of vitamin D supplementation on dengue virus replication, Toll-like receptor expression, and cytokine profiles on dendritic cells.

Dengue, caused by dengue virus (DENV) infection, is a public health problem worldwide. Although DENV pathogenesis has not yet been fully elucidated, the inflammatory response is a hallmark feature in severe DENV infection. Although vitamin D (vitD) can promote the innate immune response against virus infection, no studies have evaluated the effects of vitD on DENV infection, dendritic cells (DCs), and inflammatory response regulation. This study aimed to assess the impact of oral vitD supplementation on DENV-2 infection, Toll-like receptor (TLR) expression, and both pro- and anti-inflammatory cytokine production in monocyte-derived DCs (MDDCs). To accomplish this, 20 healthy donors were randomly divided into two groups and received either 1000 or 4000 international units (IU)/day of vitD for 10 days. During pre- and post-vitD supplementation, peripheral blood samples were taken to obtain MDDCs, which were challenged with DENV-2. We found that MDDCs from donors who received 4000 IU/day of vitD were less susceptible to DENV-2 infection than MDDCs from donors who received 1000 IU/day of vitD. Moreover, these cells showed decreased mRNA expression of TLR3, 7, and 9; downregulation of IL-12/IL-8 production; and increased IL-10 secretion in response to DENV-2 infection. In conclusion, the administration of 4000 IU/day of vitD decreased DENV-2 infection. Our findings support a possible role of vitD in improving the innate immune response against DENV. However, further studies are necessary to determine the role of vitD on DENV replication and its innate immune response modulation in MDDCs.

Exploring the potential enzymatic bioremediation of vermicompost through pesticide-detoxifying carboxylesterases.

Vermicompost is a known biofertilizer of potential use in soil bioremediation. This study was undertaken to explore the capacity of grape marc-derived vermicompost to inactivate methyl carbamate (MC) and organophosphorus (OP) pesticides via exploring the carboxylesterase (CE) activity level and its response to pesticide exposure. We first optimized the method for enzyme activity assay comparing the CE activity in two contrasting homogenization procedures (30-min mixing and mortar grinding). Thereafter, we assessed the sensitivity of the enzyme by both in vitro and vermicompost incubation trials with selected pesticides. The main findings can be summarized as follows: i) grinding the vermicompost in water (2% w/v) yielded maximum enzyme activity; ii) at concentrations around 10-4 M, highly toxic oxygen-analog metabolites of OPs strongly inhibited the CE activity (76-93% inhibition), but MC did not inhibit the enzyme activity; iii) liquid vermicompost was able to degrade chlorpyrifos and inactivate its highly toxic metabolite chlorpyrifos-oxon. Our results suggest that liquid vermicompost is the most appropriate preparation to increase the enzymatic potential of vermicompost in pesticide-contaminated soils.

Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection.

BACKGROUND: HIV-1 induces an uncontrolled inflammatory response of several immune components, such as inflammasomes. These molecular complexes, associated with Toll-like receptor (TLR) activity, induce the maturation and release of IL-1ß and IL-18 and eventually induce pyroptosis. It has been previously demonstrated that HIV induces inflammasome activation, which is significantly lower in the gastrointestinal tissue and blood from people living with HIV-1 with spontaneous control of viral replication. Therefore, immunomodulatory agents could be useful in improving HIV prognosis. OBJECTIVE: To evaluate the potential inhibitory effect of sulfasalazine (SSZ) on inflammasomes and TLRs in peripheral blood mononuclear cells (PBMCs) from people living with HIV and healthy donors. METHODS: PBMCs were obtained from 15 people living with HIV and 15 healthy donors. Cells were stimulated with agonists of TLRs and inflammasomes and subsequently treated with SSZ. The concentration of IL-1ß and the relative expression of NLRP3, NLRC4, NLRP1, AIM2, ASC, Caspase-1, IL-1ß, and IL-18 were quantified. RESULTS: Cells treated with SSZ exhibited a decreased IL-1ß production after inflammasome and TLR stimulation, as well as regulation of inflammasome-related genes, in both people with HIV and healthy individuals. The concentration of IL-1ß was positively correlated with the CD4+ T-cell count and negatively with the viral load. CONCLUSION: Our results suggest that SSZ has an immunomodulatory effect on inflammasome and TLR activation that depends on the clinical HIV status.

Terrestrial birds in coastal environments: metabolic rate and oxidative status varies with the use of marine resources.

Life in saline environments represents a major physiological challenge for birds, particularly for passerines that lack nasal salt glands and hence are forced to live in environments that do not contain salty resources. Increased energy costs associated with increased salt intake, which in turn increases the production of reactive oxygen species, is likely a major selection pressure for why passerines are largely absent from brackish and marine environments. Here we measured basal metabolic rates (BMR) and oxidative status of free-ranging individuals of three species of Cinclodes, a group of passerine birds that inhabit marine and freshwater habitats in Chile. We used a combination of carbon, nitrogen, and hydrogen isotope data from metabolically active (blood) and inert (feathers) tissues to estimate seasonal changes in marine resource use and infer altitudinal migration. Contrary to our expectations, the consumption of marine resources did not result in higher BMR values and higher oxidative stress. Specifically, the marine specialist C. nigrofumosus had lower BMR than the other two species (C. fuscus and C. oustaleti), which seasonally switch between terrestrial and marine resources. C. fuscus had significantly higher total antioxidant capacity than the other two species (C. nigrofumosus and C. oustaleti) that consumed a relatively high proportion of marine resources. Nearly all studies examining the effects of salt consumption have focused on intraspecific acclimation via controlled experiments in the laboratory. The mixed results obtained from field- and lab-based studies reflect our poor understanding of the mechanistic link among hydric-salt balance, BMR, and oxidative stress in birds.

Response of digestive enzymes and esterases of ecotoxicological concern in earthworms exposed to chlorpyrifos-treated soils.

Assessment of organophosphorus (OP) pesticide exposure in non-target organisms rarely involves non-neural molecular targets. Here we performed a 30-d microcosm experiment with Lumbricus terrestris to determine whether the activity of digestive enzymes (phosphatase, ß-glucosidase, carboxylesterase and lipase) was sensitive to chlorpyrifos (5 mg kg-1 wet soil). Likewise, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were measured in the wall muscle and gastrointestinal tissues as indicators of OP exposure. Chlorpyrifos inhibited the acid phosphatase (34% of controls), carboxylesterase (25.6%) and lipase activities (31%) in the gastrointestinal content. However, in the gastrointestinal tissue, only the carboxylesterase and lipase activities were significantly depressed (42-67% carboxylesterase inhibition in the foregut and crop/gizzard, and 15% lipase inhibition in the foregut). Chlorpyrifos inhibited the activity of both cholinesterases in the gastrointestinal tissues, whereas the AChE activity was affected in the wall muscle. These results suggested chlorpyrifos was widely distributed throughout the earthworm body after 30 d of incubation. Interestingly, we found muscle carboxylesterase activity strongly inhibited (92% of control) compared with that detected in the gastrointestinal tissues of the same OP-exposed individuals. This finding was explained by the occurrence of pesticide-resistant esterases in the gastrointestinal tissues, which were evidenced by zymography. Our results suggest that digestive processes of L. terrestris may be altered by chlorpyrifos, as a consequence of the inhibitory action of the insecticide on some digestive enzymes.

Left-right asymmetry in firing rate of extra-retinal photosensitive neurons in the crayfish.

The purpose of this paper is to explore the firing rate of the caudal photoreceptors (CPRs) from the sixth abdominal ganglion of the crayfish Cherax quadricarinatus. We use simultaneous extracellular recordings on left and right CPR in the isolated ganglion (n = 10). The CPRs showed an asymmetry in the spontaneous activity and light-induced response. In darkness, we observed one subgroup (70%) in which the left CPR (CPR-L) and right CPR (CPR-R) had spontaneous firing rates with a median of 18 impulses/s and 6 impulses/s, respectively. In another subgroup (20%), the CPR-R had a median of 15 impulses/s and the CPR-L had 8 impulses/s. In both groups, the differences were significant. Furthermore, the CPRs showed an asymmetrical photoresponse induced by a pulse of white light (700 Lux, 4 s). In one subgroup (30%), the CPR-L showed light-induced activity with a median of 73%, (interquartile range, IQR = 51), while the CPR-R had a median of 41%, (IQR = 47). In another subgroup (70%), the CPR-R showed a median of 56%, (IQR = 51) and the CPR-L had a median of 42%, (IQR = 46). In both groups, the differences were significant. Moreover, we observed a differential effect of temperature on CPR activity. These results suggest a functional asymmetry in both activities from left and right CPRs. These CPR activity fluctuations may modulate the processing of information by the nervous system.

Effects of chlorpyrifos on soil carboxylesterase activity at an aggregate-size scale.

The impact of pesticides on extracellular enzyme activity has been mostly studied on the bulk soil scale, and our understanding of the impact on an aggregate-size scale remains limited. Because microbial processes, and their extracellular enzyme production, are dependent on the size of soil aggregates, we hypothesized that the effect of pesticides on enzyme activities is aggregate-size specific. We performed three experiments using an Andisol to test the interaction between carboxylesterase (CbE) activity and the organophosphorus (OP) chlorpyrifos. First, we compared esterase activity among aggregates of different size spiked with chlorpyrifos (10mgkg-1 wet soil). Next, we examined the inhibition of CbE activity by chlorpyrifos and its metabolite chlorpyrifos-oxon in vitro to explore the aggregate size-dependent affinity of the pesticides for the active site of the enzyme. Lastly, we assessed the capability of CbEs to alleviate chlorpyrifos toxicity upon soil microorganisms. Our principal findings were: 1) CbE activity was significantly inhibited (30-67% of controls) in the microaggregates (<0.25mm size) and smallest macroaggregates (<1.0 - 0.25mm), but did not change in the largest macroaggregates (>1.0mm) compared with the corresponding controls (i.e., pesticide-free aggregates), 2) chlorpyrifos-oxon was a more potent CbE inhibitor than chlorpyrifos; however, no significant differences in the CbE inhibition were found between micro- and macroaggregates, and 3) dose-response relationships between CbE activity and chlorpyrifos concentrations revealed the capability of the enzyme to bind chlorpyrifos-oxon, which was dependent on the time of exposure. This chemical interaction resulted in a safeguarding mechanism against chlorpyrifos-oxon toxicity on soil microbial activity, as evidenced by the unchanged activity of dehydrogenase and related extracellular enzymes in the pesticide-treated aggregates. Taken together, these results suggest that environmental risk assessments of OP-polluted soils should consider the fractionation of soil in aggregates of different size to measure the CbE activity, and other potential soil enzyme activities.

[Effects of prebiotics and probiotics on gastrointestinal tract lymphoid tissue in hiv infected patients]. / Efecto de la terapia con probióticos/prebióticos sobre la reconstitución del tejido linfoide asociado a la mucosa gastrointestinal durante la infección por el virus de la inmunodeficiencia humana-1.

HIV infection induces alterations in almost all immune cell populations, mainly in CD4+ T cells, leading to the development of opportunistic infections. The gut-associated lymphoid tissue (GALT) constitutes the most important site for viral replication, because the main target cells, memory T-cells, reside in this tissue. It is currently known that alterations in GALT are critical during the course of the infection, as HIV-1 induces loss of tissue integrity and promotes translocation of microbial products from the intestinal lumen to the systemic circulation, leading to a persistent immune activation state and immune exhaustion. Although antiretroviral treatment decreases viral load and substantially improves the prognosis of the infection, the alterations in GALT remains, having a great impact on the ability to establish effective immune responses. This emphasizes the importance of developing new therapeutic alternatives that may promote structural and functional integrity of this tissue. In this regard, therapy with probiotics/prebiotics has beneficial effects in GALT, mainly in syndromes characterized by intestinal dysbiosis, including the HIV-1 infection. In these patients, the consumption of probiotics/prebiotics decreased microbial products in plasma and CD4+ T cell activation, increased CD4+ T cell frequency, in particular Th17, and improved the intestinal flora. In this review, the most important findings on the potential impact of the probiotics/prebiotics therapy are discussed.

Earthworm-induced carboxylesterase activity in soil: Assessing the potential for detoxification and monitoring organophosphorus pesticides.

Soil enzyme activities are attracting widespread interest due to its potential use in contaminant breakdown, and as indicators of soil deterioration. However, given the multiple environmental and methodological factors affecting their activity levels, assessment of soil pollution using these biochemical endpoints is still complex. Taking advantage of the well-known stimulatory effect of earthworms on soil microbes, and their associated enzyme activities, we explored some toxicological features of carboxylesterases (CbEs) in soils inoculated with Lumbricus terrestris. A microplate-scale spectrophotometric assay using soil-water suspensions was first optimized, in which kinetic assay parameters (Km, Vmax, dilution of soil homogenate, and duration of soil homogenization) were established for further CbE determinations. Optimal conditions included a soil-to-water ratio of 1:50 (w/v), 30-min of shaking, and 2.5mM of substrate concentration. As expected, CbE activity increased significantly in soils treated with L. terrestris. This bioturbed soil was used for exploring the role of CbE activity as a bioscavenger for organophosphorus (OP) pesticides. Soil treated with two formulations of chlorpyrifos revealed that CbE activity was a significant molecular sink for this pesticide, reducing its impact on soil microbial activity as shown by the unchanged dehydrogenase activity. Dose-dependent curves were adjusted to an exponential kinetic model, and the median ecological dose (ED50) for both pesticide formulations was calculated. ED50 values decreased as the time of pesticide exposure increased (14 d-ED50s=20.4-26.7 mg kg(-1), and 28 d-ED50s=1.8-2.3 mg kg(-1)), which suggested that chlorpyrifos was progressively transformed into its highly toxic metabolite chlorpyrifos-oxon, but simultaneously was inactivated by CbEs. These results were confirmed by in vitro assays that showed chlorpyrifos-oxon was a more potent CbE inhibitor (IC50=35.5-4.67 nM) than chlorpyrifos (0.41-0.84 µM). The results showed that earthworm-induced CbE activity is an efficient bioscavengers for OP pesticides, acting as a soil safeguarding system. Moreover, the simple dose-response curves against OP exposure suggest that this enzyme--combined with other enzyme activities (e.g., dehydrogenase)--may be a suitable biomarker of pesticide exposure.

HIV-1 induces the first signal to activate the NLRP3 inflammasome in monocyte-derived macrophages.

BACKGROUND/AIMS: Inflammasomes are multimolecular complexes that regulate caspase-1. They act as sensors for endogenous and exogenous signals, and mediate the processing of pro-IL-1ß into its secreted, biologically active form. The NLRP3 inflammasome and IL-1ß are particularly interesting because they are required for efficient control of viral infections. Indeed, HIV-1 induces expression of NLRP3 and IL-1ß in healthy controls, but not in HIV-1-infected patients. Here we evaluate whether HIV-1 can induce activation of the NLRP3 inflammasome. METHODS: Human primary monocyte-derived macrophages were infected with HIV-1 in the absence or presence of classical NLRP3 inflammasome activators, and IL-1ß release was assessed by ELISA. RESULTS: HIV-1 initiates the priming signal for NLRP3 inflammasome activation through the NF-κB-associated pathway in human primary monocyte-derived macrophages. Furthermore, priming of NLRP3 activation in response to HIV-1 was independent of the viral envelope, since similar results were observed with HIV-1 and pseudotyped HIV-1 lacking the env gene. CONCLUSION: Our findings suggest that HIV-1 infection promotes IL-1ß secretion by inducing the first signal for NLRP3 inflammasome activation, a phenomenon that may contribute to AIDS progression.

Effectiveness of Drug Repurposing and Natural Products Against SARS-CoV-2: A Comprehensive Review.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the COVID-19 pandemic, causing respiratory disorders, and even death in some individuals, if not appropriately treated in time. To face the pandemic, preventive measures have been taken against contagions and the application of vaccines to prevent severe disease and death cases. For the COVID-19 treatment, antiviral, antiparasitic, anticoagulant and other drugs have been reused due to limited specific medicaments for the disease. Drug repurposing is an emerging strategy with therapies that have already tested safe in humans. One promising alternative for systematic experimental screening of a vast pool of compounds is computational drug repurposing (in silico assay). Using these tools, new uses for approved drugs such as chloroquine, hydroxychloroquine, ivermectin, zidovudine, ribavirin, lamivudine, remdesivir, lopinavir and tenofovir/emtricitabine have been conducted, showing effectiveness in vitro and in silico against SARS-CoV-2 and some of these, also in clinical trials. Additionally, therapeutic options have been sought in natural products (terpenoids, alkaloids, saponins and phenolics) with promising in vitro and in silico results for use in COVID-19 disease. Among these, the most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin and betulinic acid, which were proposed as SARS-CoV-2 inhibitors. Among the drugs reused to control the SARS-CoV2, better results have been observed for remdesivir in hospitalized patients and outpatients. Regarding natural products, resveratrol, curcumin, and quercetin have demonstrated in vitro antiviral activity against SARS-CoV-2 and in vivo, a nebulized formulation has demonstrated to alleviate the respiratory symptoms of COVID-19. This review shows the evidence of drug repurposing efficacy and the potential use of natural products as a treatment for COVID-19. For this, a search was carried out in PubMed, SciELO and ScienceDirect databases for articles about drugs approved or under study and natural compounds recognized for their antiviral activity against SARS-CoV-2.